Optically active substituted pyridinylmethyl sulfinyl-benzimidazole enantiomers and their pharmaceutically acceptable salts are proton pump inhibitors, which are useful as antiulcer agents. These compounds include omeprazole, lansoprazole, rabeprazole, pantoprazole, pariprazole and leminoprazole.
There are several patents and patent applications disclosing oxidation of prochiral sulfide. U.S. Pat. No. 6,166,213 describes a process for the preparation of omeprazole by oxidation of pyrmetazole in the presence of meta chloroperoxybenzoic acid. U.S. 2003/0171591 discloses a method of producing benzimidazoles comprising oxidizing sulfide with an excess of oxidizing agent in the presence of a catalyst for asymmetric induction. U.S. Pat. No. 6,229,021 describes a process for the preparation of omeprazole comprising oxidizing its corresponding thioether with peroxyacetic acid in a two-phase water and chlorinated organic solvent medium. U.S. Pat. No. 6,268,502 describes a process for the preparation of omeprazole comprising oxidizing its corresponding thioether with 3-chloroperoxybenzoic acid in ethyl acetate. U.S. Pat. No. 6,603,009 discloses a process for the preparation of omeprazole comprising oxidizing its corresponding thioether with sodium percarbonate and molybdenum salt catalyst. U.S. Pat. No. 5,386,032 claims a process for the preparation of omeprazole comprising oxidizing its corresponding thioether with m-chloroperoxybenzoic acid at specific pH. PCT application WO 99/47514 discloses a method of producing benzimidazole compounds comprising oxidizing its corresponding thioether with perborate salt.
PCT application WO 03/089408 describes an enantioselective catalytic oxidation of sulfide with an oxidizing agent, in an organic solvent, base and in the presence of titanium or vanadium complexed with a monodentate ligand. Toluene is used in Example 1 of WO 03/089408 as an organic solvent. In general, it should be noted that solvents are used in excess and as a liquid that dissolves the solid to make a solution. Thus, if the amount of a purported solvent is too low to dissolve all the reactants and reagents, it is not considered to be a solvent. In this manner, for example, an organic compound can be used either as a solvent if it is provided in excess or only as a base if it is not provided in a quantity sufficient to function as a solvent.
U.S. Pat. No. 5,948,789 describes oxidation of a pro-chiral sulfide with an oxidizing agent and chiral titanium complex in an organic solvent. Each and every reference in the prior art literature of which the inventors are aware discloses the use of organic solvent in the catalytic oxidation.